α-d-Glucopyranoside, β-d-fructofuranosyl, benzoate

Repeated dose toxicity: dermal

Administrative data

Endpoint:

repeated dose toxicity: dermal, other

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

The study is flagged as a critical study for SIDS endpoint in report on benzoates. Bibliographic source of article: Matthews E. J., Environm. Health Perspec. 101 [Suppl 2], 347-482 (1994)

Data source

Reference

Reference Type:

other: SISD Assessment report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: Not specified

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Benzoic acid

EC Number:

200-618-2

EC Name:

Benzoic acid

Cas Number:

65-85-0

Molecular formula:

C7H6O2

IUPAC Name:

benzoic acid

Test material form:

not specified

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Administration / exposure

Type of coverage:

open

Vehicle:

not specified

Details on exposure:

Four male and four female rabbits were used in each treatment group and in the control group. The skin of one-half of the animals was abraded and the others left intact. Benzoic acid was applied 5 days a week for 3 weeks at dosage levels of 100, 500, 2500 mg/kg bw.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

21 days

Frequency of treatment:

Benzoic acid was applied 5 days a week for 3 weeks

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Remarks:

Controls

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

500 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

2 500 mg/kg bw/day (nominal)

No. of animals per sex per dose:

4

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

The rabbits were observed daily for signs of dermal irritation and changes in general behavior and appearance. Individual body weights were recorded weekly. Hematologic and biochemical studies were conducted once in the
pretest period and again at 21 days of the study. Gross and histopathology was performed on liver, kidneys, thyroid/parathyroid, heart, lung, ovaries, testes, adrenals as well as most gastrointestinal tract and neurological organs.

Sacrifice and pathology:

Gross and histopathology was performed on liver, kidneys, thyroid/parathyroid, heart, lung, ovaries, testes, adrenals as well as most gastrointestinal tract and neurological organs.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

effects observed, treatment-related

Description (incidence and severity):

Very slight dermal irritation was noted for one rabbit at the 2500 mg/kg dosage level.

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Details on results:

Very slight dermal irritation was noted for one rabbit at the 2500 mg/kg dosage level. No compound-related effects were seen in general behavior and appearance, body weight, clinical laboratory tests, organ weights, or survival.

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

2 500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

dermal irritation

Target system / organ toxicity

Key result

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

The repeated dose toxicity of dermal exposure to benzoic acid was determined in New Zealand white rabbits in a 21 day study. No compound-related effects were seen in general behavior and appearance, body weight, clinical laboratory tests, organ weights, or survival. The NOAEL was set to 2500 mg/kg/day.

Executive summary:

The repeated dose toxicity of dermal exposure to benzoic acid was determined in New Zealand white rabbits. Four male and four female rabbits were used in each treatment group and in the control group. The skin of one-half of the animals was abraded and the others left intact. Benzoic acid was applied 5 days a week for 3 weeks at dosage levels of 100, 500, 2500 mg/kg bw. The rabbits were observed daily for signs of dermal irritation and changes in general behavior and appearance. Individual body weights were recorded weekly. Hematologic and biochemical studies were conducted once in the pretest period and again at 21 days of the study. Gross and histopathology was performed on liver, kidneys, thyroid/parathyroid, heart, lung, ovaries, testes, adrenals as well as most gastrointestinal tract and neurological organs. Result: Very slight dermal irritation was noted for one rabbit at the 2500 mg/kg dosage level. No compound-related effects were seen in general behavior and appearance, body weight, clinical laboratory tests, organ weights, or survival. The NOAEL was set to 2500 mg/kg/day.